Despite a wealth of data indicating that opioids can modulate the immune system, little is known regarding the neural mechanisms that underlie the immune alterations induced by drug related cues. The current proposal seeks to further establish and extend our recent finding that environmental stimuli that had been previously associated with heroin delivery elicit immune alterations similar to those observed with actual heroin use. More specifically, we have demonstrated that heroin associated environmental stimuli induce alterations in the induction of nitric oxide similar to those observed with heroin. This proposal seeks to elucidate the role of the cholinergic system within the basolateral amygdala in these effects. Specific Aim I tests the hypothesis that the conditioned effects of heroin on nitric oxide expression are mediated through the basolateral amygdala. Specific Aim II tests the hypothesis that the alterations in nitric oxide production seen with exposure to a previously drug-associated environment involve the cholinergic system within the basolateral amygdala. Specific Aim Ml tests whether the conditioned effects of heroin on nitric oxide production will be evident in a live infection and whether antagonism of cholinergic receptors within the basolateral amygdala will reverse these alterations. Collectively, the proposed studies will provide innovative and important new data regarding the neural mechanisms underlying the immunomodulation elicited by drug related cues. [unreadable] [unreadable] [unreadable]